The trouble with the risk of teratoma presents a stem cell paradox.
Stem cells possess two traits lacking in other cells: self-renewal and pluripotency. This duo of defining functions is key to the ability of stem cells to be used to treat patients via regenerative medicine. A paradox exists because while self-renewal and pluripotency are both needed for stem cells to be clinically useful, these cellular traits also are crucial factors in determining how likely stem cells are to cause tumors as a side effect. I have done a CIRM video (see the filming above) on this critical issue, which you can watch here.
Stem cells have the ability to self-renew, meaning to make more stem cells. One stem cell becomes two, two become four, four become eight, and so on. Since stem cells divide at least once a day, pretty soon you have millions of stem cells. Without self-renewal, scientists could never expand stem cells to the number needed for treatments.
Stem cells also must be pluripotent. What pluripotent means is that stem cells have the power to give rise to other cell types. The ‘pluri’ part of the word pluripotent means that stem cells can give rise to multiple other cell types. Like self-renewal, pluripotency is a critical property of stem cells for their potential use in regenerative medicine.
A general rule is that the more self-renewing and pluripotent a type of stem cell is, the more tumorigenic it will be. What this means is that the better potential job a stem cell can do in regenerating a tissue, most often means the riskier that cell type is to use because of its propensity to form tumors.
The two most exciting and promising types of stem cells for regenerative medicine–hESC and hIPS cells–are both highly pluripotent and readily self-renew. Perhaps not surprisingly, both of these cell types almost without exception are highly tumorigenic. Both hESC and hIPSC are in fact defined in many cases by their ability in preclinical studies to form a type of tumor called a ‘teratoma’. While teratoma are most often benign, you can imagine if a patient develops dozens of them in a particular tissue the end result could be tragic. Teratoma can also be malignant as well.
What this means is that researchers working to develop stem cell-based therapies are in a peculiar situation. They must first show that the hESC or hIPSC they are using can form teratoma since that is a defining characteristic, but then they must differentiate and/or purify these cells by flow cytometry to a point such that the scientists can now prove to the FDA that the cells completely lack any ability to form teratoma.
What we need are methods to tease apart tumorigenicity from pluripotency and self-renewal. The ideal stem cell would be highly pluripotent and possess robust self-renewing properties, but not form teratoma. Is that even possible? I don’t know, but until we solve the teratoma problem, every regenerative medicine therapy based on hESC or hIPSC will be impeded.